GENETIC VARIANT CORE SUMMARY Chronic pain is a complex problem, likely influenced by multiple environmental and genetic factors. Growing evidence for a genetic basis for developing chronic pain suggests it may be possible to use genetic predictors to differentiate between patients likely to be susceptible versus resilient to the development of chronic pain. This project is the Genetic Variant Core (GVC) of the Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program. In this Program, the Clinical Centers will recruit and collect clinical data and biofluid samples from two longitudinal cohorts of 1800 subjects each. Biofluid samples will be collected 0, 3, and 6 months after an acute pain episode, consisting of a specific surgical procedure or a specific musculoskeletal trauma. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers. For the proposed Genetic Variant Core, Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Program to establish the final study design and protocols. All of the A2CPS Program investigators will work together to establish the 40 primary outcome biomarkers. The ODGC and Clinical Center investigators will jointly decide on the specific sample type(s) and collection/processing/storage methods. The ODGC and Data integration Resource Center/Data Coordination Component (DIRC/DCC) investigators will establish Metadata and Data Standards and a workflow for submission of metadata and data to the DCC. The GVC and the Administrative Core of the ODGC will establish an integrated LIMS for sample and data tracking, and recording of metadata. The GVC and DIRC/Data Integration and Analysis Component (DIAC) will establish data analysis pipelines. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on DNA isolation and genetic variant arrays for the 3600 participant samples that will be collected by the Clinical Centers. Aim 3 will encompass submission of metadata and data to the DIRC/DCC, quality control of the data, and data analysis and interpretation. The primary goal of this Component is generation and submission of high-quality gene variant array data for the validation of pre-selected genetic variant biomarkers. While the study is not powered to identify novel genetic associations, we expect to extend the analysis beyond the jointly selected genetic variant biomarkers to include additional variants implicated in susceptibility/resilience to chronic pain. GVC component investigators will participate in integrative analyses with the DIRC/DIAC aimed at developing pain signatures comprised of multiple biomarker types (including molecular, clinical, psychosocial, and/or imaging biomarkers) indicating susceptibility/resilience to chronic pain, which can be used to develop personalized strategies for prevention and treatment of chronic pain. The personnel for this proposed GVC have acquired the necessary skills and knowledge to successfully execute this project from participation in multiple large-scale projects generating genetic variant array data.